Nonclinical precedent Request an invite
Atlas/Bispecific antibodies/Talvey/Safety margin

Talvey: what safety margin did regulators accept?

talquetamab · GPRC5D x CD3
Check my plan vs. these
Safety margin at NOAEL
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
NOAEL / key findings
No adverse effects up to 30 mg/kg weekly (highest dose); transient lymphocyte decrease, increased globulins, fibrinogen, IL-10
“No adverse effects on any toxicology or safety pharmacology parameter evaluated at up to the high dose of 30 mg/kg weekly”
✓ VerifiedFDA multi-discipline review, p. 55Source ↗

Same question, other bispecifics

Blincyto

blinatumomab · CD19 x CD3
Chimpanzee exposure (Cmax 0.9-1.36 ng/mL) higher than human Css at 9 and 28 µg/day; no NOAEL or multiple stated

Columvi

glofitamab · CD20 x CD3
Monkey exposure below clinical: AUC multiples 0.03-0.28 in studies without obinutuzumab pretreatment

Elrexfio

elranatamab · BCMA x CD3
Monkey NOAEL/LOEL 0.3 mg/kg exposure well below human exposure (0.1x or 0.2x)

Epkinly

epcoritamab · CD20 x CD3
Monkey SC NOAEL 10 mg/kg: 5x clinical steady-state AUC; IV 1 mg/kg exposure equal to clinical AUC

Hemlibra

emicizumab · FIXa x FX
Monkey NOAEL (30 mg/kg, 26-week) ~11x human AUC at 3 mg/kg QW

Korjuny

catumaxomab · EpCAM x CD3
No margin: surrogate BiLu mouse NOAEL (0.2-3.0 µg/kg) equivalent to the clinical catumaxomab dose (1.43 µg/kg)

Lunsumio

mosunetuzumab · CD20 x CD3
No NOAEL; CRS and infections in monkeys at exposures 0.008-1.84x human AUC

Rybrevant

amivantamab · EGFR x MET
Monkey AUC at 120 mg/kg 5x human AUC at the 1050 mg clinical dose

Tecvayli

teclistamab · BCMA x CD3
Monkey NOEL 30 mg/kg IV weekly: 22x AUCtau, 48x Cmax vs human 1.5 mg/kg SC weekly

Vabysmo

faricimab · VEGF-A x Ang-2
Ocular NOAEL 0.5 mg/eye (6-month monkey): exposure margin only around 1x human

Ziihera

zanidatamab · HER2 x HER2 (biparatopic)
Monkey NOAEL 150 mg/kg: exposure ~10-fold above clinically relevant exposure

Bizengri

zenocutuzumab · HER2 x HER3
Not stated in public reviews

Imdelltra

tarlatamab · DLL3 x CD3
Not stated in public reviews

Kimmtrak

tebentafusp · CD3 x gp100 (TCR fusion)
Not stated in public reviews

Lynozyfic

linvoseltamab · BCMA x CD3
Not stated in public reviews

Ordspono

odronextamab · CD20 x CD3
Not stated in public reviews

Removab

catumaxomab · EpCAM x CD3
Not stated in public reviews

Summary across all 18 bispecifics →